Analytical True Positive Versus Clinical False Positive

The assumption underlying interpretation of a drug test result is the accuracy and reliability in the analysis and identification of the drug or drug metabolite present in the urine. The standard urine drug test protocol involves an initial test using a battery of immunoassays. The accuracy of an immunoassay is determined by the immunospeci-ficity of the assay antibody, and immunoassays in general do not have strict specificity for the target drug or drug metabolites. Many immunoassays have demonstrable reactivities with structurally similar compounds, some of which are not illicit drugs or are not abused. Moreover, some immunoassays may even detect substances that are structurally unrelated to the target analyte (e.g., PCP assay detects dextromethorphan) (1,2). This limitation of specificity of immunoassays is well recognized, and this awareness has led to two important tenets of urine drug testing programs: (a) the positive result of an immunoassay is only a presumptive positive result and (b) definitive identification of the drug or the metabolite must be based on a second test, the confirmation test. Laboratorians and clinicians are familiar with the concepts that an initial positive result by immunoassay could be a false positive and that confirmation testing resolves the uncertainty surrounding the first test and definitively identifies the drug or its metabolites.

Healthcare providers who make clinical or management decisions based on drug test results do so because of the confidence they have that a positive result confirmed by the laboratory is a true positive. But a confirmed positive result is only an analytical true positive, while it can be a clinical false positive. This is because the presence of a drug or drug metabolite in the urine documents only that the individual has been exposed to the drug but warrants no inference about the nature of the exposure or the reason for the positive test. The person may very well have a valid explanation for producing the positive drug test, for example, he or she is on a prescription medication containing codeine, which can account for the positive codeine and morphine results. In the context of the reason for drug testing, this analytical true positive result may wrongly implicate the person as an illicit drug user. Hence, this gas chromatography-mass spectrometry (GC-MS) confirmed analytical true positive result is a clinical false positive case. The converse of this is when the individual cannot give a credible explanation for the analytical true positive result, in which case the test result is not only an analytical true positive, but it is also a clinical true positive in the sense that the drug test has identified illicit drug use. Thus, recognizing a positive result to be a clinical false positive eliminates the wrongful implication, with grave consequences to the person, that the individual is an illicit drug user. This can be accomplished, in some cases, by additional laboratory testing (e.g., 6-acetylmorphine testing for morphine positive results), and in every instance with a thorough medical review conducted by a qualified physician.